Human Cystic Fibrosis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE2395 | GEO | 2005/03/10
SECONDARY ACCESSION(S): PRJNA91595
REPOSITORIES: GEO
Similar Datasets
Project description:Summary: CF patients homozygous for the DF08 DF08 genotype present a full range of phenotypic manifestations that exist within the pulmonary system. This project aims to identify candidate genes that influence the severity of pulmonary disease; Hypothesis: The goal is to find genes predictive of progression in CF. More information can be found at http://www.hopkins-genomics.org/cf/cf001/index.html
2007-10-24 | E-GEOD-2395 | biostudies-arrayexpress
Project description:In clinical routine, the diagnosis of cystic fibrosis (CF) is still a challenge due to the limitations of diagnosis guidelines and tests. A diagnosis test of choice, the sweat test measures eccrine sweat chloride concentration as a byproduct of the eccrine sweat gland CFTR function. Despite the combined use of CFTR genotyping and direct physiologic testing of CFTR function, reports of inconclusive diagnosis justified the need for alternative tests and new biomarkers. Meanwhile, eccrine sweat composition has already been linked to disease-specific profiles of non-electrolytes (i.e. proteins, peptides and metabolites). In this study, we analyzed sweat samples from 28 healthy volunteers and 14 CF patients by UHPLC-Q-Orbitrap-based Shotgun proteomics, to address CF-related changes in sweat protein composition and abundance. Over 1000 proteins were identified and quantified in a label-free manner. Beside similar protein composition, enrichment and functional classifications, HV and CF samples were grouped apart since protein abundance profiles were significantly correlated with CF status and degree of severity (ΔF508 homozygous and pancreatic insufficiency onset). Four-hundred and two proteins in CF-specific abundance, 68 proteins in genotype-specific abundance and 71 proteins in abundance related to pancreatic status, respectively, highlighted eccrine gland cell perturbations in protein biosynthesis & trafficking, CFTR proteostasis & membrane stability, cell-cell adherence, membrane integrity & cytoskeleton crosstalk. Cytoskeleton-related biomarkers were of utmost interest because of consistent abundances between CF sweat and other CF tissues. Nine clinical CF diagnosis biomarker (CUTA, ARG1, EZR, AGA, FLNA, MAN1A1, MIA3, LFNG, SIAE) and 5 CF severity biomarker (ARG1, GPT, MDH2, EML4 (ΔF508 homozygous), MGAT1 (pancreatic insufficiency)) candidates were deemed suitable for further verification.
2022-10-13 | PXD028518 | Pride
Project description:Cystic fibrosis (CF) is one of the commonest lethal genetic diseases in which the role of microRNAs (miRNAs) has yet to be explored. We hypothesized that unique miRNA expression profiles exist in CF versus non-CF bronchial epithelial cells so the our aim was to investigate whether unique miRNA expression profiles exist in CF, particularly in CF bronchial epithelial cells and explore their effects on influencing signaling pathways.
2010-03-23 | GSE19431 | GEO
Project description:Using the 450K BeadChIP, we profiled DNA methylation in nasal epithelial cells collected from CF patients homozygous for the CFTR p.Phe508del mutation and healthy controls. We replicated DNA methylation at CpG sites by pyrosequencing. Patients were stratified according to their lung function (forced expiratory volume in 1 second). Our study (i) points to the importance of genes responsible for the integrity of the epithelium and the inflammatory and immune responses to explain lung disease variability in CF, (ii) highlights new candidate genes potentially involved in lung disease severity, while it corroborates the role of known modifier genes, and (iii) suggests that CF-associated dynamic changes of DNA methylation are prominent in transcriptionally active genomic regions. Bisulphite converted DNA from the 48 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
2018-07-31 | GSE101641 | GEO
Project description:Cystic fibrosis (CF) is one of the commonest lethal genetic diseases in which the role of microRNAs (miRNAs) has yet to be explored. We hypothesized that unique miRNA expression profiles exist in CF versus non-CF bronchial epithelial cells so the our aim was to investigate whether unique miRNA expression profiles exist in CF, particularly in CF bronchial epithelial cells and explore their effects on influencing signaling pathways. The expression of 667 miRNAs were measured in bronchial brushings from individuals with and without cystic fibrosis (CFn=5, non-CF n=5). The 5 CF patient samples have been normalised to the controls so we get a final normalised value for 5 samples only. There are 2 raw data files for samples and controls as there are two cards A and B ran for each sample, for a total of 4 raw data files available on the Series record.
2010-03-22 | E-GEOD-19431 | biostudies-arrayexpress
Project description:Heritable genetic variants modify cystic fibrosis (CF) clinical phenotypes, e.g., lung disease, age-of-onset of persistent Pseudomonas aeruginosa (P. aeruginosa), and meconium ileus (MI). Previous genome wide association studies (GWAS) have begun to inform the genetic architecture of CF phenotypes. Analyses of gene expression will complement GWAS, as demonstrated by analyses of gene expression in lymphoblastoid cell lines (LCLs) to identify disease-related pathophysiological processes for non-CF complex traits. In this study, global gene expression was measured in RNA from LCLs from 754 CF patients and analyzed for association with lung disease severity, age-of-onset of persistent P. aeruginosa pulmonary infection, and MI at birth. Each phenotype displayed distinct expression associations. Most pathways significantly associated with lung disease were related to membranes, vesicle traffic, and Golgi/endoplasmic reticulum (ER). Pathways containing HLA genes (Class I and II) were significantly associated with both lung and P. aeruginosa phenotypes, but they displayed qualitative differences between phenotypes. MI associated with pathways involving oxidative phosphorylation. The results support the concept that gene expression associated with heritable variation acts to modify phenotypes in CF. 754 samples were analyzed; 2 control samples were plated by Expression Analysis per plate and 1 pooled sample from the patient set was added to one well on each plate.
2016-05-19 | E-GEOD-60690 | biostudies-arrayexpress
Project description:Cystic fibrosis (CF) is an inherited, multi-system disease caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a ubiquitous ion channel important for epithelial hydration. A direct consequence of this dysfunction is impaired mucociliary clearance, chronic airway infection and a persistent neutrophilic inflammatory response that results in progressive loss of lung function, development of respiratory failure and premature death. Partial restoration of CFTR function is now possible for most CF patients through mutation specific CFTR modulators. Ivacaftor monotherapy produces significant clinical improvement in CF patients with the G511D mutation. Dual therapy, combining ivacaftor with lumacaftor or tezacaftor, results in modest clinical improvements in patients homozygous for F508del. More recently, triple therapy with elexacaftor/tezacaftor/ivacaftor (ETI) has led to dramatic improvements in lung function and quality of life in patients homozygous and heterozygous for F508del. Sputum proteomics is a powerful research technique capable of identifying important airway disease mechanisms by interrogating the proteome, an entire set of proteins within biological samples. It has confirmed the central role of neutrophilic immune dysregulation in CF and non-CF bronchiectasis, particularly involving the release of antimicrobial proteins and neutrophil-extracellular traps (NETs), and through impaired anti-inflammatory mechanisms. These processes produce distinct molecular signatures within the sputum proteome that become increasingly abnormal with chronic airway infection and progressive lung disease severity. In CF patients, airway and systemic inflammatory cytokines potentially related to these signatures reduce with the various forms of CFTR modulation. To date, no studies of ETI therapy in CF lung disease have assessed large-scale change in protein expression using untargeted proteomics. We hypothesised that ETI therapy would shift the sputum proteome toward health, potentially normalising airway biology in people with CF. The objectives of this study were to investigate changes in the CF sputum proteome with the introduction of ETI, correlate these with changes in clinical markers of disease severity, and make comparisons with the sputum proteome in healthy controls and in repeat samples from CF patients not suitable for ETI therapy. We also explored which molecular pathways associated with CF lung disease did not change with ETI.
2023-11-14 | PXD041950 | Pride
Project description:Heritable genetic variants modify cystic fibrosis (CF) clinical phenotypes, e.g., lung disease, age-of-onset of persistent Pseudomonas aeruginosa (P. aeruginosa), and meconium ileus (MI). Previous genome wide association studies (GWAS) have begun to inform the genetic architecture of CF phenotypes. Analyses of gene expression will complement GWAS, as demonstrated by analyses of gene expression in lymphoblastoid cell lines (LCLs) to identify disease-related pathophysiological processes for non-CF complex traits. In this study, global gene expression was measured in RNA from LCLs from 754 CF patients and analyzed for association with lung disease severity, age-of-onset of persistent P. aeruginosa pulmonary infection, and MI at birth. Each phenotype displayed distinct expression associations. Most pathways significantly associated with lung disease were related to membranes, vesicle traffic, and Golgi/endoplasmic reticulum (ER). Pathways containing HLA genes (Class I and II) were significantly associated with both lung and P. aeruginosa phenotypes, but they displayed qualitative differences between phenotypes. MI associated with pathways involving oxidative phosphorylation. The results support the concept that gene expression associated with heritable variation acts to modify phenotypes in CF.
2016-05-19 | GSE60690 | GEO
Project description:This multi-center study will compare multi-target DNA and quantitative FIT stool-based testing to colonoscopy in individuals with Cystic Fibrosis (CF) undergoing colon cancer screening with colonoscopy. The primary endpoint is detection of any adenomas, including advanced adenomas and colorectal cancer (CRC).
| 2726863 | ecrin-mdr-crc
Project description:Cystic fibrosis (CF) remains a life-shortening disease without a definitive cure. Novel therapeutics targeting the causative defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are now in clinical use. Lumacaftor/ivacaftor is a CFTR modulator approved for patients homozygous for the CFTR mutation p.Phe508del, but there are wide variations in treatment responses preventing prediction of patient responses. We aimed to determine changes in gene expression related to treatment initiation and response. Whole-blood transcriptomics was performed using RNA-Seq in 20 patients with CF pre- and 6 months post-lumacaftor/ivacaftor (drug) initiation and 20 non-CF healthy controls. Correlation with clinical variables was performed by stratification via clinical responses. We identified 491 genes that were differentially expressed in CF patients (pre-drug) compared with non-CF controls. In addition, 36 genes were differentially expressed when comparing pre-drug to post-drug profiles within CF patients. Transcriptomics revealed novel pathways in CF patients at baseline compared to non-CF, and in clinical responders to lumacaftor/ivacaftor. Overall changes in gene expression post-lumacaftor/ivacaftor were modest compared to pre-drug CF profiles.
2019-01-03 | GSE124548 | GEO